Project Summary Peripheral nerve injury can lead to anomalous sensations referred to as neuropathic pain. Nerve injury may result from a variety of insults ranging from frank injury to the nerve though sectioning or compression, and is particularly prevalent following chemotherapies used in oncology. Symptoms often include continuous burning pain and abnormal sensory sensations such as allodynia (pain as a result of non-noxious stimuli) and hyperalgesia (an increased response to a normally painful stimulus) Persistent pain after resolution of clinically appreciable signs of injury poses a therapeutic challenge and current therapies do not meet this medical need. Accordingly, novel treatment options that afford additional benefit in prevention or relief of pain are needed. In this proposal, a collaboration initiated between the University of California San Diego (UCSD) and Epigen Biosciences Inc. seeks to fully evaluate the apoA-I binding protein (AIBP), an agent that interferes with inflamed lipid rafts in spinal glia and has been found to reverse facilitated pain states in several mouse models. The goals of this proposal during the R21 phase include the AIBP protein manufacture and characterization, pharmacokinetics studies, design and refinement of experimental animal protocols to assess efficacy and pharmacodynamics of AIBP in mouse models of polyneuropathy (induced by chemotherapeutic agents) and mononeuropathy (L5 nerve ligation), and optimization of pharmacodynamics assays to evaluate AIBP engagement of spinal glia and its anti-inflammatory effects. Contingent upon the successful completion of a set of proposed milestones, the R33 phase will commence to establish dose-dependent efficacy profile for AIBP treatment of neuropathic pain and to correlate it with AIBP pharmacokinetics and pharmacodynamics. The proposal is designed to advance the AIBP project to the point where it can meet the entry criteria for NINDS Cooperative Research to Enable and Advance Translational Enterprises (CREATE) program, with the ultimate goal to develop a novel biologic therapeutics for management of persistent pain states.